2016_BT PROSTATE CANCER COURSE BOOK

Teaching course on BRACHYTHERAPY FOR PROSTATE CANCER

Course Director: P. HOSKIN

Teaching staff: B. AL-QAISIEH J.-M. COSSET S. MACHTENS F.-A. SIEBERT Contouring Administrator: C. SALEMBIER Local organiser: G. GOLDNER Project Manager: G. AXELSSON

Brussels, Belgium 5-7 June 2016

ACKNOWLEDGEMENTS

ESTRO the European Society for Radiotherapy and Oncology wishes to thank:

Eckert & Ziegler BEBIG : www.bebig.com Elekta : www.elekta.com Varian Medical Systems: www.varian.com

For their support and collaboration in the promotion of the course

This course includes delineation workshops performed in the framework of the Falcon platform

16 th ESTRO Teaching Course on BRACHYTHERAPY FOR PROSTATE CANCER

Introduction Welcome to the beautiful city of Brussels for the 16 th ESTRO Prostate Brachytherapy Course. Over the last few years more and more younger men have been diagnosed with localised potentially curable prostate cancer. While radical prostatectomy remains the gold standard for treatment in many countries, there is an increasing interest in the role of brachytherapy which proves a much simpler alternative and achieves similar outcomes with less risk of severe side effects. Several thousand patients now have the treatment each year in Europe. Prostate brachytherapy is not something that can be taken up by a solitary enthusiast. It requires a significant amount of team work and there needs to be careful attention to patient selection, techniques of implantation and quality assurance to ensure that optimum outcomes can be achieved. A very experienced teaching staff in all aspects of both HDR and LDR Brachytherapy will be present at the meeting and will be happy for you to ask questions both during or after the lectures. Please make use of their expertise. We hope that the teaching course will provide a foundation to begin the steep learning curve towards the achievement of consistent high quality implants and that more patients will have the option to choose this form of treatment. On behalf of the teaching staff, Peter Hoskin, Course Director

Teaching staff:

BA

Dr. Bashar AL-QAISIEH Medical Physics and Engineering St James's Institute of Oncology Bexley Wing, St James's Hospital, Beckett Street Leeds LS9 7TF, United Kingdom Tel: +44.113.2067409 bashar@medphysics.leeds.ac.uk

JMC Dr Jean-Marc COSSET Unité de Curiethérapie

Institut Curie 26 rue d’Ulm

752048 Paris, France Tel : +33 1 44 324 622 jean-marc.cosset@curie.net

PH

Prof. Peter HOSKIN Mount Vernon Hospital Rickmansworth Road HA6 2RN Northwood Middlesex, United Kingdom Tel: + 44 1.923.844.533 peterhoskin@nhs.net

SM

Dr. med. Stefan MACHTENS Marien-Krankenhaus Bergisch Gladbach, Klinik für Urologie Dr. Robert-Koch-Str. 18, 51465 Bergisch Gladbach, Germany Tel. 49 02202 / 938-2310 stefan.machtens@mkh-bgl.de

FAS Frank-André SIEBERT (PhD)

Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Strahlentherapie (Radioonkologie)

Arnold-Heller-Str. 9 24105 Kiel, Germany Tel:+ 49 431/597-3022 siebert@onco.uni-kiel.de

Contouring Administrator:

CS

Dr. Carl SALEMBIER Europe Hospitals - Site St Elisabeth Department of Oncology Avenue De Fré 1180 Brussels, Belgium c.salembier@europehospitals.be

NOTE TO THE PARTICIPANTS OF THE ESTRO TEACHING COURSE ON BRACHYTHERAPY FOR PROSTATE CANCER The present texts and slides are provided to you as a basis for taking notes during the course. In as many instances as practically possible, we have tried to indicate from which author these slides have been borrowed to illustrate this course. It should be realised that the present text can only be considered as notes for a teaching course and should not in any way be copied or circulated. They are only for personal use. Please be very strict in this as it is the only condition under which such services can be provided to the participants of the course.

Disclaimer

This course has been accredited by ACOE/UEMS

The faculty of the teachers for this event has disclosed any potential conflict of interest that the teachers may have.

Course Director: P. HOSKIN

Teaching staff: B. AL-QAISIEH J.-M. COSSET S. MACHTENS F.-A. SIEBERT Contouring Administrator: C. SALEMBIER

ESTRO TEACHING COURSE ON BRACHYTHERAPY FOR PROSTATE CANCER Brussels, Belgium 5-7 June 2016

Teaching staff B Al-Qaisieh JM Cosset P Hoskin S Machtens C Salembier FA Siebert Sunday June 5 09:00-09:10 09:10-09:30 09:30-10:00 10:00-10:30

BA

JMC

PH SM CS

FAS

Welcome and introduction Prostate anatomy for brachytherapy Patient Selection for LDR seed brachytherapy Patient Selection for HDR seed brachytherapy

PH SM

JMC

PH

10:30-11:00

BREAK

11:00-11:30 11:30-12:30

QA for brachytherapy

BA

LDR seed techniques and video demonstrations

CS/JMC SM/BA

12:30-13:30

LUNCH

13:30-14:30 14:30-15:30

HDR techniques and video demonstrations

PH/FAS

CTV definition

CS

15:30-16:00

BREAK

16:00-16:30 16:30-17:00

Imaging for prostate brachytherapy Image registration and planning principles:

SM

FAS/BA

17:00-17:30

Review and interactive session

Monday June 6 09:00-09:40 09:40-10:30

Clinical results of LDR Clinical results of HDR

CS PH

10:30-11:00

BREAK

11:00-1200 12:00-13:00

Interactive session: planning HDR & LDR Post plan imaging, dosimetry and implications

ALL

FAS/CS

13:00-14:00

LUNCH

14:00-14:40 14:40-15:30

Complications of prostate brachytherapy Management of toxicity and complications

SM SM

15:30-16:00

BREAK

16:00-17:00

Radiation protection

JMC

1700-1730

Review and interactive session:

Tuesday June 7 09:00-10:30

Focal therapy: concepts and LDR

JMC/SM

Focal therapy: HDR

PH

10:30-11:00

BREAK

11:00-11:30 11:30-12:00 12:00-12:30

Brachytherapy for salvage

JMC

Prostate brachytherapy: LDR, HDR, surgery or IMRT

PH All

Final discussion session

A New and Improved Membership Programme Bringing you more benefits & online services

ESTRO MEMBERSHIP 2013

BECOME AN ESTRO MEMBER TODAY AND JOIN THE RADIATION ONCOLOGY COMMUNITY

ESTRO has renewed its membership categories for 2013 in order to bring you more benefits that are better suited to your needs. ESTRO’s mission is to guide your day-to-day professional development and to disseminate all the latest findings and knowledge that are crucial to our rapidly evolving field. Join ESTRO, become an integral part of the Radiation Oncology Community. New for 2013!

The Society has the mission to represent all the Radiotherapy professionals: Radiation Oncologists, Medical Physicists in the field of Radiotherapy, Radiobiologists and RTT (Radiotherapy Technologists). Membership is also open to other oncology specialists such as Medical Oncologists, Surgeons, Nuclear Medicine Physicians... By joining ESTRO, you will receive numerous benefits that have been carefully designed to support and advance your career. We invite you to peruse the many Membership categories on offer and to sign-up for the one that is best tailored to meet your professional requirements.

The European SocieTy for Radiotherapy & Oncology (ESTRO), with its active community of over 5000 members, has supported the role of Radiation Oncology within the multidisciplinary treatment of cancer for more than 30 years. ESTRO is the ideal platform for the sharing of cutting-edge knowledge and ground-breaking know-how within the radiation oncology community. ESTRO provides numerous high- level educational opportunities through teaching courses, organises conferences and congresses that are at the forefront of our specialisation, and is responsible for several top-notch publications.

ESTRO is developing additional new online services which will be functional as of Jan- uary 2013: through our new search engine you will be able to access a comprehensive e-library containing documents such as the Green Journal and conference abstracts, webcasts, posters, free access to FALCON (our delineation tool), our newsletter, etc.

Don’t forget that you can register for the 2013 ESTRO conferences and teaching courses at a discounted rate as soon as you have signed up for your 2013 membership!

“The new communication tools and on-line services create a personalised platform to help ESTRO members connect and network. Moreover, ESTRO members will find an environment that will stimulate education and development. As such the new membership categories will be an important part of the strategy of realising the central vision statement of ESTRO by offering the necessary tools for the individual member to develop his or her professional skills in the interests of our patients.”

Dirk Verellen, ESTRO Membership Officer

How can you become an ESTRO member?

Please apply online via the ESTRO website www.estro.org. You can also contact the ESTRO office by email or by phone for any assistance you may require.

Tel.: +32 2 775 93 40 Fax: +32 2 779 54 94 Email: membership@estro.org Website: www.estro.org

ESTRO Rue Martin V, 40 1200 Brussels Belgium

Individual membership | full

Individual membership | Associate

In Training member This category is open to all European healthcare providers who are active in the field of Radiation Oncology, as well as related areas in a non-commercial setting. In training members must be under the age of 35 , have relevant professional experience or a university diploma granted less than 5 years ago, and currently be in training. Affiliate member This category is available for Radiation Oncology professionals and/ or individuals interested in the field of Radiation Oncology who do not require full involvement in the society but who still wish to enjoy some of the more basic benefits on offer. Corporate Representative This category is reserved for individual members working for a company.

Full Membership is open to all healthcare providers who are active in the field of cancer care and/or cancer research, as well as related areas in a non-commercial setting. Active member Active Membership is open to all Radiation Oncology professionals. This category entitles you to the most complete range of benefits that the Society has on offer. Supporting Ambassador Membership This category is reserved for individuals who are strongly committed to the Society and who want to take an extra step to help ESTRO develop further by paying a higher membership fee. The additional income generated by these big-hearted members will be used to create a solidarity fund. The fund will be available to sponsor the membership fee of less fortunate individuals, finance support grants for ESTRO events, and help to ensure that Radiation Oncology professionals from economically challenged countries are also able to participate in our scientific arena.

ESTRO membership runs from the 1st of January to the 31st of December. N.B.: Please note these important changes: RTTs will now belong to all membership categories without distinction of disciplines. When registering for courses or conferences, whatever the mem- bership category they belong to, RTTs will benefit from the ‘In Training’ rate.

Packages of benefits for individual members

FULL MEMBERSHIP

supporting Ambassador | 250€

A A

B B

C C

D D

E

will benefit from will benefit from

+ +

+ +

+ +

+

Active member | 95€

ASSOCIATE MEMBERSHIP In Training member | 75€ Affiliate member | 55€

A A A

B B

C

will benefit from will benefit from will benefit from

+ +

+

Corporate representative | 55€

A

Eligibility for Grants, Awards and Fellowships Eligibility for Working Groups, Task Force Groups, and Faculties Eligibility to hold formal positions such as President, being on the Board of Directors, Councils, Standing Committees, and participation in ESTRO’s Governance Activities Access to the Membership Directory Access to the “Members area” on the ESTRO website enabling you to read and/or upload your presentations and research, etc. Voting rights in the General Assembly D

Subscription to the Green Journal Discounted price for ESTRO Publications and Handbooks

Online access to ESTRO Handbooks Subscription to the ESTRO Newsletter Access to Conference Abstract Books Access to ESTRO Guidelines Access to the ESTRO Annual Reports

A

All the benefits listed above + Reduced registration fee for one ESTRO Conference or teaching course of choice per year (incl. joint conferences and courses)

B

E

Eligibility for Awards Access to the “Members area” on the ESTRO website (read only) Access to Job advertisements Access to the ESTRO Annual Reports Reduced subscription rate to the European Journal of Cancer

Online access to educational materials Contribution to the ESTRO Ambassador Solidarity fund (acknowledgement in the ESTRO webpage) Access to FALCON Cases (basic and endorsed cases) Access to the Webcast library (immediate access)

B

All the benefits listed above + the possibility to get either a re- duced registration fee for one ESTRO Conference or teaching course of choice (incl. joint conferences and courses) or a Grant once per year

Other categories ESTRO can choose to bestow the following membership categories upon specially selected individuals. Neither of these memberships can be signed-up for. Honorary Membership Honorary Members are professionals who have made a noteworthy contribution towards ESTRO’s mission. They are selected by the Nominating Council of ESTRO. Dual Membership This category can be granted to individual members who benefit from a JOINT mem- bership agreement. The agreements are signed on a case-by-case basis between ESTRO and a National Society; the membership fee is covered by the annual fee paid by the partnering Society. The member is entitled to the same benefits as an Affili- ate Member (with the exception that the discounted rate for attending courses and conferences is not limited to just one a year).

C

Reduced fee for attending ESTRO and Joint Conferences Reduced fee for attending ESTRO and Joint Courses Eligibility for Grants and Awards Eligibility to participate in ESTRO’s Governance Activities Access to FALCON Cases (basic) Access to the Webcast library (after 6 months)

C

All the benefits listed above + Access to Membership Directory (young corner)

INSTITUTIONAL membership

Institutional Membership is available for institutes who are willing to purchase several individual memberships in batch for their members. Your institute can buy several individual memberships (all benefits included) and enjoy additional benefits such as registration packages for online workshops, a dedicated corner in the Newsletter, the opportunity to disseminate standards/guidelines within the organisation and much more. Read the full details of all package deals available for institutes and the related list of benefits on www.estro.org or contact the ESTRO office by e-mail: institutional-membership@estro.org.

ESTRO MOBI ITY GRANTS (TTG) Visit another institute L In order to learn about or gain experience with a technique, equipment or its application that is not easily available in your institute and which would be useful to you and your department, you can visit another institute for one to three weeks, in Europe or outside.

Just apply for an ESTRO Mobility Grant, the so-called “Technology Transfer Grants” (TTG).

Next deadline: 31 October 2016

Check the selection criteria on www.estro.org

WELCOME TO ESTRO PROSTATE BRACHYTHERAPY IN BRUSSELS

ESTRO, Brussels G b i ll A l a r e a xe sson

Y t h our eac ers ……………..

• Peter Hoskin:

Mount Vernon, UK

• Bashar AlQaisieh: • Jean Marc Cosset: • Stefan Machtens: • ar a em er: • Frank Andre Siebert: C l S l bi

Leeds

Paris, Fr

Bergisch Gladbach,DE

B l BE russe s,

Kiel, DE

Our exhibitors

• BSM • Nucletron • Varian

Age specific incidence rates UK 2009/11

A St d di d I id R t UK 1993 2011 ge- an ar se nc ence a es, , , -

Cancer incidence and mortality, males, Europe: 2010

IARC

http://www.cancerresearchuk.org/cancer-info/cancerstats/world/incidence/#By

Age standardised incidence and mortality rates Europe 1975-2011 Incidence

Mortality

Worldwide A t d di d i id ge s an ar se nc ence and mortality rates 2010

IARC

182,123 men in SEER database

• Peer review evidence based trees estimate:

RP: 24% (15-30) EBRT: 58% (54-64%) BT: 9 6% (6 17 9%) . - .

Actual utilisations rates: •

RP 13 44% : - EBRT: 43-56% BT: 1.8-10.9%

Lo w

Intermediate

High

Prostate Brachytherapy: Anatomy

S. Machtens Director of the Department of Urology and Paediatric Urology Academic Teaching Hospital Marien-Hospital Bergisch Gladbach

With Courtesy from Geert Villeirs UZ Gent

ESTRO T hi

C B h th f P t t C eac ng ourse on rac y erapy or ros a e ancer Brussels, June 05th-07th 2016

The Prostate

The prostate surrounds the urethra and is situated below the bladder. The prostate produces fluid that is needed by sperms to move.

P thi arasympa c nerves

Course of neurovascular bundle

Nerve and vascular pathways

Zonal Anatomy C t l Gl d en ra an

Periurethral Glands (paracoronal view)

P i th l Gl d er ure ra an s

Zonal Anatomy C t l Gl d en ra an

Transition Zone (transverse view)

Transition Zone

Zonal Anatomy C t l Gl d en ra an

Central Zone

Central Zone

(paracoronal view)

Zonal Anatomy Overview

Peripheral Zone (paracoronal view)

Peripheral Zone

Zonal Anatomy O i verv ew

Anterior

AFS

Fibromuscular Stroma

(paracoronal view)

Ultrasound Normal Anatomy

CG

PZ

PZ

Isoechoic PZ C A l Hypo/hyperechoic CG orpora my acea

Ultrasound Normal Anatomy

Urethra

Urethra Sagittal

Zonal anatomy in MRI and Ultrasound

Ultrasound Normal Anatomy

Seminal Vesicles Convoluted Hypoechoic Cystic Structures

Ultrasound S itt l

th l t ag a : ure ra measuremen s

ULTRASOUND – Dorsal vein plexus

Ultrasound Prostate Carcinoma

Hypoechoic nodule compared to normal PZ Low specificity (atrophy, prostatitis, ...)

Anatomy Prostate

CG

CG

PZ PZ

PZ

PZ

PZ

PZ

Prostatic Apex Midprostate Prostatic Base

Imaging of Prostate Cancer Endorectal Coil Imaging

Endorectal Coil

60 cc

Imaging of Prostate Cancer Body coil versus Endorectal coil

Normal Prostate with Body Coil

Normal Prostate with Endorectal Coil

Imaging of Prostate Cancer Tumour Presence (Endorectal Coil)

Peripheral Zone Tumour

Peripheral Zone Tumour with Endorectal Coil

with Body Coil

Imaging of Prostate Cancer Tumour detection @ 3 Tesla

Courtesy: Fütterer JJ, Nijmegen

Kim J Comput Assist Tomogr 2006;30:7-11 (70%) , Heijmink, Radiology 2007;244:184

1 5 Tesla MRI . MRI: • Resolution: good • Contrast: good, especially soft tissue contrast

Zentrale Zone

Periphere Zone

Tumor

1 5 T .

T2-weigthed

T1-weighted

3 0 Tesla MRI .

T1 weighted

T2 -weighted

3.0 Tesla MRI + Endorectal coil

Anatomy Hyperplasia

CG

CG

CG

PZ

PZ

Benign Prostatic Hyperplasia

Variation of bladder neck according to BPH

Anatomy Urethra

External Sphincter

U thre ra

Sagittal

Coronal

Transverse

Anatomy Seminal Vesicles

T

ransverse

C l orona

Anatomy Periprostatic Structures

S

P

IO

IO

L

L

P

IO

IO

ugd

i

i

c c B

i

i

R

L

L

Transverse

Coronal

Variation in Genitourinary diaphragm

ESTRO Course Brussels 2016

S l ti ti t f t t e ec on o pa en s or pros a e cancer permanent implant brachytherapy f

Jean-Marc Cosset, Institut Curie, Paris, France

• A brief history; • The initial ABS recommendations (1999) • The ESTRO recommendations ( ) 2000 • The progressive evolution • The 2012 ABS d i recommen at ons

• Int. J. Radiation Oncology Biol. Phys., Vol. 44, No. 4, pp. 789–799, 1999

• AMERICAN BRACHYTHERAPY SOCIETY (ABS) RECOMMENDATIONS FOR TRANSPERINEAL PERMANENT BRACHYTHERAPY OF PROSTATE CANCER • SUBIR NAG, M.D.,*† DAVID BEYER, M.D.,*‡ JAY FRIEDLAND, M.D.,* § PETER GRIMM, D.O.,*\ AND RAVINDER NATH, PH D *¶ . .

1999 AMERICAN BRACHYTHERAPY SOCIETY (ABS) RECOMMENDATIONS FOR TRANSPERINEAL PERMANENT BRACHYTHERAPY OF PROSTATE CANCER • Brachytherapy as Monotherapy: • Stage T1 to T2a and • Grade Gleason sum 2–6 and • PSA < 10 ng/ml • (i e Low risk patients) . , -

1999 AMERICAN BRACHYTHERAPY SOCIETY (ABS) RECOMMENDATIONS FOR TRANSPERINEAL PERMANENT BRACHYTHERAPY OF PROSTATE CANCER

• Clinical Exclusion Criteria: • Life expectancy < 5 years • Large or poorly healed TURP defect • Unacceptable operative risks • Distant metastases

• Relative Contraindications for Brachytherapy (1) : • These patients are not ideal candidates for b h h b h h l b rac yt erapy, ut ave nevert e ess een successfully implanted. Beginners should not implant these patients. • Patients at increased risk of developing complications • Large median lobes • Previous pelvic irradiation • High AUA score • History of multiple pelvic surgeries • Severe diabetes with healing problems

• Relative Contraindications for B h h ( ) rac yt erapy 2 : • Technical difficulties which may result in inadequate dose coverage • Previous ( large ?) transurethral resection of prostate (TURP) • Gland size > 60 cc at time of implantation • Prominent median lobe P iti i l i l • os ve sem na ves c es

• Brachytherapy as a Boost to EBRT: • Stage Clinical T2b, T2c or d l • Gra e: G eason sum 8–10 or • PSA > 20 ng/ml • Other possible indications for Brachytherapy as a Boost to EBRT: • Perineural invasion • Multiple positive biopsies • Bilateral positive biopsies • MRI positive for capsular penetration

• a e .

T bl 2 ABS

i ti d id li prescr p on ose gu e nes *

B h h d f • rac yt erapy ose or monot erapy y • 125I (pre TG-43) 160 ( ) • 125I TG-43 144 • 103Pd 115–120 h (G )

• *It should be recognized that the prescription dose is different from the dose actually delivered to the entire prostate .

• Brachytherapy (including Boosting EBRT) in Conjunction with Androgen Deprivation:

P ti t ith i iti ll l t t ( 6 ) • a en s w n a y arge pros a e > 0 cc that have downsized sufficiently

The ESTRO recommendations

• The 2000 Dan Ash paper : Radiother Oncol 2000 Dec;57(3):315 21 • . - . • ESTRO/EAU/EORTC recommendations d i l i f on permanent see mp antat on or localized prostate cancer. • Ash D, Flynn A, Battermann J, de Reijke T, Lavagnini P, Blank L; ESTRO/EAU Urological Brachytherapy Group; EORTC Radiotherapy Group.

• Actually only minor differences with the ABS paper …

Clinical e cl sion criteria x u :

• Life expectancy < 5 years • Large or poorly healed TURP defect • Unacceptable operative risks Bl di di d ti • ee ng sor er or an coagu a on a cannot be stopped • Distant metastases • Prostate volume greater than 50 cc ( 60 ?) at the time of implantation l ti th t

Relative contra-indications :

• Large median lobes • Previous pelvic irradiation • High AUA score ( IPSS > 15) • History of multiple pelvic surgery

1999 2016 ; the evolution ! -

• Ideas progressively changed … • Risk groups ; should brachytherapy as monotherapy be reserved to low-risk patients ? • What about age ? • What about the biopsies ?( Percentage of involved samples, microfoci, bilaterality …) • What about median lobes and obstructive syndroms ? • Which role for MRI ?

i k h ld b h h • R s groups ; s ou rac yt erapy as monotherapy be reserved to low- risk patients ?

• Problems with the risk groups : • Several definitions !

The imagepartwith relationship ID rId2wasnot found in the file.

The main question :

• The intermediate risk group : • suitable for brachytherapy as monotherapy ?

• Brachytherapy. 2007 Jan-Mar;6(1):2-8.  Interstitial implant alone or in combination with l b di i h f i di i k externa eam ra at on t erapy or nterme ate-r s prostate cancer: a survey of practice patterns in the United States. Frank SJ , Grimm PD , Sylvester JE , Merrick GS , et al . PURPOSE Thi t d i i d t d t di : s s u y s a me a un ers an ng and defining the current patterns of care with respect to prostate brachytherapy for patients

with intermediate-risk localized disease in the combined academic and community setting.

 RESULTS I th b

: n e a sence o

f PNI ll f , a o

those surveyed would perform h f i di i k monot erapy or nterme ate-r s patients, GS 7 (3+4) or PSA 10-20, with T d % c 1c an <30 cores +…  CONCLUSIONS: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant.

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• IJRO 2008  Purpose: The aim of this study was to analyze overall and relapse- f i l i h t f 8 ti t % f h ree surv va s n a co or o 09 pa en s, 34 o w om corresponded to a higher risk group than ABS criteria.

• For this Institut Curie series ; • Low risk patients - • and

• « Favorable intermediate » patients ; PSA between 10 and 15 and all other • , low-risk criteria • Or ; • Gleason 7 and all other low risk criteria , -

2008 Paper

LOW INT

The 2016 Institut Curie experience ( i P ) n ress f • Up ate on 675 pat ents, a w t a o ow-up o more than 10 years d i ll i h f ll

No difference in long term overall survival - …

• Conclusions ( 2008, confirmed in 2016) • Our results suggest that at least selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed permanent implant brachytherapy as monotherapy.

2008 G it i i ASC0 en o-ur nary sympos um, - ASTRO,SUO Congress, February 2008 • Abstract 238, Linstadt et al (USA); • Intermediate-risk patients; brachytherapy alone : • 5-year bNED 96 % Thi i li i l • « s ser es c n ca success compares favorably with the results d i h d li i reporte us ng ot er mo a t es … »

• ABS Meeting , 2009 h •

i PO 65 : t e PMH exper ence PO 101 : the Seattle experience Both favor Brachytherapy as monotherapy for intermediate-

• • • • •

risk patients

Seattle ; 9-year BRFS of 91.9 % …

• Finally to make a long story short ; , • The Prostate Cancer Results Study Group P t G i t l ( • e er r mm e a ., 2011-2012 BJU) • With upgrade received every year !

Comparing Treatment Results Of PROSTATE CANCER Prostate Cancer Results Study Group 2016

Peter Grimm, DO Prostate Cancer  Center of Seattle

31

INTERMEDIATE RISK RESULTS weighted 40 th f ll l th 100 ti t > mon s o ow-up or ess an pa en s

LDR SEEDS ALONE

EBRT + ADT

100

66 54

56 55 49

59 111 169

104

13

+ Seeds + ADT Robot RP

23 24

14

37

35

79

158

111

15 92

153 156

165

90

98

151

34

96 168

44

161 109

40

n Free

4

57

Brachy Seeds Alone Hypo EBRT EBRT & Seeds

16

36 167 99 82 152

38

68

69

58

105 30

25

HDR

97 77 107

45

71 81 8373 72

39

12

160 11

27

6

80

42

31

51

91

156

108

64

3

43

63

62

17

47

86

18

50 93

95 65

28

74 78

67 70 76 88 75

150

90

157 EBRT & SEEDS

5 7

9 26

ressio 70

52

Success

Surgery EBRT CRYO

152

155

103

29

102

154

41

159

100

1

85 110 60

Surgery

48

19 32

53

87

8

2

10

101

11

163

60

46

94 89 84 1164

EBRT

HIFU

eatment

A Prog

Tr

20

HDR

50

155

EBRT Seeds + ,

% PS

40 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 21 ← Years from Treatment → 80

ADT

Protons

• Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

Update of

32

6/11/2016

• Most available data thus strongly suggest that at least a subset of selected patients in the intermediate-risk group may benefit from Brachytherapy as monotherapy …

• Eur Urol. 2013 Dec;64(6):895-902. • A new risk classification system for therapeutic decision making with intermediate-risk prostate ti t d i d l t d t l cancer pa en s un ergo ng ose-esca a e ex erna - beam radiation therapy. • Zumsteg ZS 1 , Spratt DE , Pei I , Zhang Z , Yamada Y , Kollmeier M , Zelefsky MJ . • CONCLUSIONS: • Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms.

Oncology (Williston Park). 2016 Mar;30(3):229-36. Favorable vs Unfavorable Intermediate Risk Prostate - Cancer: A Review of the New Classification System and Its Impact on Treatment Recommendations. Serrano NA , Fastro MS . N l ifi i h • ew c ass cat on systems ave been proposed that modify the i i N i l C h i ex st ng at ona ompre ens ve Cancer Network guidelines and h bdi id i h t at su v e men w t intermediate-risk prostate cancer i f bl d f bl nto avora e an un avora e subgroups

Oncology (Williston Park). 2016 Mar;30(3):229-36. Favorable vs Unfavorable Intermediate Risk Prostate Cancer: A - Review of the New Classification System and Its Impact on Treatment Recommendations. Serrano NA , Fastro MS .

• What about age ?

• In the early years most groups were , reluctant to propose brachytherapy alone to « young » ( < 60 years ?) patients, • Mostly because of the lack of long follow-up …

• However, since that time …

• Cancer J. 2006 Jul-Aug;12(4):305-8. • The effect of age on prostate implantation results. • Peschel RE, Khan A, Colberg J, Wilson LD. CONCLUSIONS: • • Patients who are 60 years of age or younger h d i h l d id d w o are treate w t u trasoun -gu e transperineal prostate implantation can t bi h i l di f expec 5-year oc em ca sease- ree survival rates similar to those of older patients treated with ultrasound guided - transperineal prostate implantation therapy.

• Am J Clin Oncol. 2008 Dec;31(6):539-44. • Biochemical and functional outcomes following brachytherapy with or without supplemental therapies in men < or = 50 years of age with clinically organ-confined prostate cancer. • Merrick GS, Wallner KE, Galbreath RW, Butler WM, Brammer SG, Allen ZA, Lief JH, Adamovich E. • CONCLUSIONS: • Men < or =50 years of age have favorable biochemical and functional outcomes following brachytherapy Depending on risk . group assignment, brachytherapy with or without supplemental therapies should be considered a viable option for all healthy men regardless of age.

• Int J Radiat Oncol Biol Phys 2010 Aug 1;77(5):1315-21 . . • Young men have equivalent biochemical outcomes compared with older men after treatment with brachytherapy for prostate cancer. • Burri RJ, Ho AY, Forsythe K, Cesaretti JA, Stone NN, Stock RG. • Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York, USA. CONCLUSION • : • Young men achieve excellent 5- and 8-year b h l l h bl ioc emica contro rates t at are compara e to those of older men after prostate brachytherapy.

• In CONCLUSION ( Burri 2010):

• “Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer”.

h b h bi ( • W at a out t e ops es ? Percentage of involved samples, microfoci, bil li ) atera ty … i • What about the impact of the percentage of positive biopsies ? • Nil for some authors ; • Pe et al Urology 2009 ., • No impact of the percentage of positive biopsies on Freedom From Biochemical Failure …

Int J Radiat Oncol Biol Phys. 2002 Mar 1;52(3):664-73. Relationship between percent positive biopsies and biochemical outcome after permanent interstitial brachytherapy for clinically organ-confined carcinoma of the prostate gland. Merrick GS 1 , Butler WM , Galbreath RW , Lief JH , Adamovich E . CONCLUSION • : • …. Our results suggest that the percentage of positive biopsies is not statistically significant in predicting the 5-year biochemical disease-free outcome for patients with low, intermediate, and high-risk disease undergoing permanent prostate brachytherapy.

• But to be taken into account for others : • Heidenreich A et al. EAU guidelines on prostate cancer. April 2010: C it i • r er a : • Stage cT1b-T2a, N0, M0 • Gleason score ≤6 7 (?) “grey area” = • Initial PSA (ng/mL)<10 • Amount of biopsy cores involved with cancer (%) ≤50 P l 3 • rostate vo ume <50 cm • IPSS ≤12

What about microfoci ?

• The « index lesion » concept ! • Treat the index ( main ) lesion and ignore the microfoci ? S i f l • ee presentat on on oca brachytherapy …

• Already quoted ; • Brachytherapy. 2007 Jan-Mar;6(1):2-8.  Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States. Frank SJ Grimm PD Sylvester JE Merrick GS et al , , , , .

« In the absence of PNI, all of those surveyed would perform

monotherapy for intermediate-risk patients GS 7 (3+4) or PSA 10-20 , , with cT1c and <30% cores +… »

What about bilaterality ?

• Depends … • Massive bilateral involvement , • or • Unilateral « index » lesion and controlateral microfoci ? • Different impact on decision !

• What about median lobes and obstructive syndroms ?

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• Brachytherapy. 2011 Jan-Feb;10(1):29-34. • One-step customized transurethral i f h d resect on o t e prostate an permanent implant brachytherapy for selected prostate cancer patients: technically feasible but too toxic. • Cosset JM Barret E Castro Pena P Cathelineau , , - , X, Galiano M, Rozet F, Pierrat N, Timbert M, Vallancien G • Department of Radiotherapy, Institut Curie, 26 rue d’Ulm, Paris, France.

Patients with prominent median lobe hyperplasia and/or high International Prostate Symptom Score (IPSS) are often contraindicated for prostate brachytherapy, mainly because of the risk of post-implant urinary retention. We evaluated an approach combining in the same operative step a limited transurethral resection (TURP) of the median lobe, immediately followed by permanent implant- free seed brachytherapy.

• METHODS AND MATERIALS:

From January 2007 to November 2008 • , 22 patients underwent a customized limited TURP of their median lobe immediately before brachytherapy.

• CONCLUSION: • Although technically feasible, with relatively few migrating seeds and satisfactory post implant - dosimetric parameters, one-step TURP and brachytherapy was found to be poorly tolerated, with higher than usual urinary retention and urinary toxicity rates. • Considering those results, our group is presently evaluating a two-step procedure with a , customized TURP followed after 4-6 months by brachytherapy. • ( Encouraging preliminary results …)

Two-step TURP and brachytherapy • Now almost a standard ; • See : • Abstracts PO37 and PO38 , ABS 2011 • PO37 ; bladder neck resection 6 k b f i l wee s e ore mp ant • PO38 ; vaporization of obstructive prostate tissue by 100W holmium laser

Which role for MRI ? • With better and better MRIs in 2015: • 3 Tesla, multiparametric, endorectal probe … A i t l f MRI • prom nen ro e or ; • Most authors now take (more and more) the MRI images into account : • Large MRI tumors, with extensive bilateral involvement and/or large « contact » with the capsule … • … might be poor candidates for brachytherapy as monotherapy …

This being said ….

• The 2012 ABS d i recommen at ons

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Risk groups

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“P ti t ith hi h b bilit f • a en s w g pro a y o organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. • Low-risk patients may be treated with PPB l ith t th d f a one w ou e nee or supplemental external beam radiotherapy. • High-risk patients should receive l t l t l b supp emen a ex erna eam radiotherapy if PPB is used.”

• Intermediate-risk patients should be considered on an individual case basis . I di i k i i h • nterme ate-r s pat ents w t favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending.

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I 2016 th i di ti n , e n ca ons o permanen implant prostate cancer brachytherapy are expanding : f t

• Towards …

At l t l t d ti t i th • eas se ec e pa en s n e intermediate risk group • Younger patients • Bilateral lesions if only controlateral microfoci • Larger prostates ( after volumetric reduction or not) • Obstructive prostate ( after t i d RTUP) cus om ze • Moreover …

New indications ;

• Brachytherapy « boost » after EBRT S l b h th ft f il • a vage rac y erapy a er a ure of EBRT (or even brachytherapy) • Focal brachytherapy • ( see ad hoc presentations)

• With a recent additional competitor ; A ti ill • c ve surve ance ….

Med Care. 2014 Jul;52(7):579-85.. Perceptions of Active Surveillance and Treatment Recommendations for Low-risk Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists. Kim SP 1 Gross CP Nguyen PL Smaldone MC Shah ND Karnes RJ , , , , , , Thompson RH , Han LC , Yu JB , Trinh QD , Ziegenfuss JY , Sun M , Tilburt JC . • CONCLUSIONS • Most prostate cancer specialists in the United States believe Active Surveillance effective and underused for low-risk prostate cancer … … yet continue to recommend the primary treatments their specialties deliver (!)

• Considering the pending and unsolved questions about Active Surveillance they could be right , (?) …

Thank you !

High dose rate brachytherapy for prostate cancer: PATIENT SELECTION

Peter Hoskin Mount Vernon Cancer Centre Northwood UK

HDR prostate brachytherapy

• Practical  Existing source, afterloading

• Physical

 Greater implant volume  i l di i l i l nc u ng sem na ves c es

• Biological  Low  /  tumour; greater biological dose with high dose per fraction

Advantages of temporary HDR prostate brachytherapy

Radioprotection

– no free live sources – no risk of source loss – no radioprotection issues after discharge

Cheap: utilises existing HDR source and equipment

D d ay case proce ure

Disadvantages of temporary HDR prostate brachytherapy

High dose rate radiation requires fractionation – no longer!?

logistics: –

• Quality assurance

Selection for HDR prostate brachytherapy

• Boost with external beam

• Monotherapy

Pre treatment investigations

• General medical assessment Prostate biopsy •

• PSA • IPSS • IEFS • Flow rate • Pelvic MRI • Staging investigations  PSA  Bone scan  (Whole body MRI)  (Choline PET)  (PSMA PET)

Indications for HDR prostate brachytherapy BOOST Where there is a significant predictive risk of t l i l i l i l t ex racapsu ar or sem na ves ca nvo vemen :

External beam

Brachytherapy

Indications for HDR prostate brachytherapy BOOST

Where there is a significant predictive risk of extracapsular or seminal vesical involvement:

T3a T3b ?T2c

Gleason 8 – 10 ?Gl 4 3 eason +

Probability of organ confined disease

[Partin 2001]

PSA 6.1-10.0

Gleason T1c

T2a

T2b

T2c

3+4

54% (49-59) 35% (30-40) 26% (22-31) 24% (17-32)

4+3

43% (35-51) 25% (19-32) 19% (14-25) 16% (10-24 )

8 10 -

37% (28 48) 21% (15 28) 15% (10 21) 13% (8 20 ) - - - -

Probability of organ confined disease

[Partin 2001]

PSA >10.0

Gleason T1c

T2a

T2b

T2c

3+4

37% (32 42) 20% (17 24) 14% (11 17) 11% (7 17) - - - -

4+3

27% (21-34) 14% (10-18) 9% (8-13)

7% (4-12 )

8-10

22% (16-30) 11% (7-15)

7% (4-10)

6% (3-10 )

E t b /HDR b t f t t x eam oos or pros a e

?The low risk patient – PSA<10ng/ml

……….what is the risk of ECE

– Gleason 6 or below (?3+4) – T2a or less

or seminal vesicle

invasion??...............

Probability of organ confined disease

[Partin 2001]

PSA 4 1 6 0 . - .

Gleason T1c

T2a

T2b

T2c

2-4

90% (78-98) 81% (63-95) 75% (55-93) 73% (52-93 )

5-6

80% (78-83) 66% (62-70) 57% (52-63) 55% (44-64 )

3+4

63% (58 68) 44% (39 50) 35% (29 40) 31% (23 41) - - - -

54 patients Gland size median 57ml; range 50-97.3ml

All dosimetric goals achieved

164 patients HDR monotherapy; median CTV volume 60mls (range 14-20

Toxicity

bRFS

Pubic arch interference

• Patient position:

 Hyperextended vs standard  Plane of prostate vs pubic arch  Table / stand positions

N dl i ti • ee e nser on

 Bend the needle?  Enter via adjacent co-ordinate

HDR PROSTATE BRACHYTHERAPY INDICATIONS

• Boost with external beam therapy  Intermediate/high risk disease  ?Low risk disease

• Monotherapy

 Phase II studies…..  Low/Intermediate/high risk disease

HDR monotherapy for prostate

? low risk patient

Intermediate risk patient

High risk patient

HDR monotherapy; published series and risk groups

LOW INT HIGH

Yoshioka et al MSKCC

X X

X

Hoskin et al MVCC

X

X

Rogers et al

X

Mark et al Texas

X X

X

P d t l S i ra a e a pa n Martinez et al Michigan

X X

X X

Demanes et al CET X X Zamboglu et al Offenbach X X

X

HDR monotherapy: what the guidelines say…………

GEC ESTRO

ABS

HDR for salvage? GEC ESTRO guidelines 2013

HDR for salvage? ABS guidelines 2013

Selection for HDR prostate brachytherapy

Boost with external beam

M h onot erapy

Salvage

Selection for HDR prostate brachytherapy …………whole gland or focal…….

Indications for consideration of focal HDR BT

– HDR BT indicated – Focal lesion identified by:

• mpMRI ‘dominant’ lesion • Template biopsy mapping

QUALITY ASSURANCE (QA) FOR PROSTATE BRACHYTHERAPY

Bashar Al-Qaisieh

O i verv ew • TG 43 and TG43-U1 • Seed & Needle Check • Template Calibration • Ultrasound Machine Check • Commissioning Planning System • Treatment Plan Check • Post Implant QA

TG 43 d TG 43 U1 an -

Report of American Association of Physicists in Medicine R di i Th C i T k G 43 a at on erapy omm ttee as roup Medical Physics, 22(2), 209-235, Feb 1995

Update of AAPM Task Group No 43 Report: A revised . AAPM protocol for brachytherapy dose calculations M di l Ph i 31 (3) 633 674 M 2004 e ca ys cs, , - ar

TG43 U1- Cl

d fi iti d ll th • ear e n ons o p ys ca quan es, an a e equations required for the calculation of dose. • Treatment planning systems. Source calibration • . • Planning systems commissioning. • Universal standards. • Theoretical and experimental recommendations. And more . • ……. f h i l titi

D(r θ)=S k ,

Λ[G(r θ)/G(r 0 , ,

θ 0

)]g(r)F(r θ) ,

S k = air kerma strength of the source Λ= dose rate constant

G(r,θ)=geometry factor

g(r)=radial dose function

F(r,θ)=anisotropy function

TG 43 U1 QAT bl - , a e

.

AL θ) (r,D D(r)





A

L

24 1 44 .

HL   

TG43

TG43 U1 -

TG43 U1-

Seed Calibration-Well chamber

Calibration every two • years. Med. Phys. 18, 1991. • Consistency check. Cs-137, Co-60

G id li u e nes “The activity of all sources should be measured and compared with the , calibration certificate supplied by the li b f b i d i i t d t supp er, e ore e ng a m n s ere o a patient”….. Medical and Dental Guidance Notes, IPEM

Seed Calibration

•Sterile sources located in MICK maga ine z - a minimum of 10% of the total or two magazine cartridges of 15 seeds, whichever is greater. • Sterile stranded sources. - a minimum of 10% of the total or two strands of 10 seeds, whichever is greater. • Loose seeds - a minimum of 10% of the total or 20 seeds, whichever is greater.

Action level if seeds are out of tolerance

Needles Check

• Verification of loaded brachytherapy needles. • Place a film on top of the needles. The radiation from the loaded needles exposes an image in the film. • The film will verify correct loading of seeds and spacers within each needle, or indicate any discrepancies or missing seeds.

Needles Check

T l C lib i emp ate a rat on

Ultrasound Template

L l f l eve o to erance s

i ± 1

mm

Guidance Template

Planning Template

Template Calibration

Ul d M hi Ch k trasoun ac ne ec A f M h i l d El t i l S f t • ssurance o ec an ca an ec r ca a e y • Distance Accuracy (vertical and horizontal) • Contrast and Brightness (Gray bar visualization) • Image Uniformity • Penetration • Lateral Resolution IPEM t 71 P i R t l 1995/2002 - repor : r ce e a . -TG –1: Goodsitt et al. Med Physics 25(8) 1998.

Clinical Commissioning of Planning System

• Test 1: Dose Point Calculation-TG 43-U1 • Test 2: Isodose Level-TG 43-U1 G • Test 3: Volume and Dose Volume-T 43-U1 • Test 4: Anisotropy Function/Line Source Calculation- TG43-U1 • Test 5: Data transfer and handling • Test 6: Stepper Depth and Angle Tracking and Accuracy Tests

Dose Point Calculation Test

• This dose calculation ifi ti t t ver ca on es uses a dose point(s) to if th l l ti ver y e ca cu a ons of the planning t Di sys em. screpancy should be within 1%.

Dose rates (cGy h -1 U -1 ) as a function of distance

0.5cm

P1

P2

S2

S1

1cm

2cm